International Harmonization of Nomenclature and Diagnostic Criteria (INHAND)INHAND Activities
INHAND Working Group Publishes Recommendations on Apoptosis and Necrosis terminology
The terms single cell necrosis and apoptosis have been used by many pathologists as synonymous terms for many years. Recent studies have indicated that the biochemical processes underlying the two findings are in fact different. Although an earlier STP committee recommended splitting individual cell necrosis into 3 categories: apoptotic, oncotic or mixed (Levin et al 1999), the recommendations have never gained widespread use by the pathology community and following recent discussions with current INHAND working groups, the need to clarify the usage of these terms has become crucial.
The GESC has encouraged the various INHAND OWGs to choose descriptive terminology rather than terminology that implies a process. It is acknowledged that there can be significant overlap of the morphological characteristics associated with single cell necrosis and apoptosis, making them very difficult, if not impossible to distinguish without using additional techniques. There are also situations where both processes occur in the same lesion.
The Apoptosis and Necrosis Working Group has recently completed their review and recommendations. The recently published article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This publication serves as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community. The specific recommendations are:
1. Use necrosis and apoptosis as separate diagnostic terms.
Published INHAND Guides
Harmonization of nomenclature and diagnostic criteria in toxicologic pathology, especially for rats and mice, has been a goal of pathologists working in the profession for many years. In the latter part of the twentieth century, several initiatives were undertaken by the STP in the United States and by the RITA data base group (Registry of Industrial Toxicology Animal—data) in Europe. Their efforts resulted in a number of internationally recognized publications: SSNDC: Guides for Toxicologic Pathology and the WHO/IARC International Classification of Rodent Tumors.
In 2005, the Strategic and Regulatory Policy Committee (SRPC) decided that the time was ripe for a revision of the earlier guides. Their proposal began:
The European Society of Toxicologic Pathology, in conjunction with RITA, endorsed the proposal in late 2005. They suggested that since RITA had recently completed a large amount of work on proliferative lesions of both rats and mice, that the project focus on non-proliferative lesions. They also offered to provide an open version of RENI (goRENI: global open Registry Nomenclature Information System (www.goreni.org) to serve as a platform. Access to goRENI is available to all members of the participating STPs (see below for further information on accessing goRENI.)
INHAND Nomenclature Project
The result of these discussions was the INHAND Proposal (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice). In 2006, the BSTP and the JSTP joined the initiative, so that the project was truly global.
The GESC (Global Editorial Steering Committee) to oversee the activities of the project. The GESC is composed of toxicologic pathologists from all of the participating societies. In addition there are several technical consultants for web and print support.
The Organ System Working Groups (OWG) are the core of the project. Each Group is responsible for producing the non-neoplastic nomenclature for their particular organ. In addition, they review the proliferative lesions already posted on goRENI and discuss them with the RITA groups so that the final nomenclature, both proliferative and non-proliferative represent the consensus of the international collaborators.
The Chair of each OWG is appointed by the GESC. Members of the group come from each of the participating Societies and may be nominated by the Chair or by the individual STPs.
There are active OWGs for all organ systems in the rodent. However, INHAND has been expanded to include non-rodent species. If you would like to volunteer to be member of an OWG, please indicate your interest by sending an email to firstname.lastname@example.org.
When an Organ System Working Group has completed a draft of its nomenclature, the draft (with illustrations) is submitted to the GESC for initial approval and then posted on goRENI. The membership of each Society is then notified that the draft is posted and available for comments for a 60 day period. After the comment period is completed, the OWG will consider the comments and prepare a final draft. This final draft is reviewed once more by the GESC and posted on goRENI
In addition to goRENI, the completed nomenclature for each organ system will be published in the official journals of the participating Societies: Toxicologic Pathology (STP and BSTP), Journal of Toxicologic Pathology (JSTP) and Experimental and Toxicologic Pathology (ESTP)
Using the goRENI Website
The goRENI website is available to all members of each of the participating STPs (in addition to Regulators). In order to access the site, a member must first apply by going to the goRENI website. The homepage will then open:
By clicking on the “this page” area of the 3rd bulleted line (If you would like to become a member of goRENI), you will be taken to the Enrollment Page:
After you submit the form, goRENI will email you a User Name and Password (after having checked with STP that you are a valid member) it is as simple as that.
goRENI has a wealth of features. In addition to written descriptions and images of both proliferative and non-proliferative lesions of rats and mice, it also includes links to the abstracts of most published references in the descriptions, the RITA trimming Guides for all organs, and the opportunity to comment on the nomenclatures while they are in draft.